Head and Neck Cancers
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Head and neck cancers are malignancies arising in the upper aerodigestive tract (this includes: lip, tongue, salivary glands, mouth, oropharynx, nasopharynx, hypopharynx, nasal cavity, and larynx). Laryngeal (voice-box) cancer is the most frequent type, accounting for about a quarter of head and neck cancers.

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Laryngeal Cancer
Hypopharyngeal Cancer
Nasopharyngeal Cancer
Oropharyngeal Cancer
Oral Cancer
Salivary Gland Cancer
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Molecular Biology of Head and Neck Cancers
Head and Neck Cacer Resources
Latest Research Publications

Head and Neck Cacer Resources (16 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Heyman S, Pirenne Y, Van Elst F, et al.
Is FNAC (fine needle aspiration cytology) a useful tool in detection of malignancy in thyroid surgery? A single institution experience.
Acta Chir Belg. 2014 Mar-Apr; 114(2):115-7 [PubMed] Related Publications
OBJECTIVE: To evaluate if FNAC (Fine Needle Aspiration Cytology) is a useful tool in the detection of malignancy in thyroid surgery. FNAC is used routinely as a preoperative diagnostic technique and surgical strategy is often adapted. But is FNAC such a good technique in defining surgical strategy?
METHODS: We retrospectively reviewed all files of 703 patients operated from 1997 till today. We obtained the results of the FNAC, the final pathological diagnosis and these data were analyzed.
RESULTS: There were 161 male and 542 female patients. 72 out 703 patients had a malignancy. 241 patients (34.3%) had a preoperative FNAC-procedure. Male patients had significantly more malignancies (p = 0.006). In 183 patients (75.9%) the FNAC was benign, 28 patients (11.6%) showed malignancy, in 15 patients (6.2%) only blood was found and 15 patients (6.2%) showed an inconclusive result. 70.1% of the patients were true negative, 5.8% were true positive, 5.8% false positive, 5.8% false negatives, 5.8% of inconclusive results were malignant on pathology. This gives a sensitivity of 50% and specificity of 92.4%.
CONCLUSIONS: The specificity of FNAC in malignancy is high (92.4%) but a sensitivity of 50% is low. With these results adaptation of surgical strategy (hemithyroidectomy or total thyroidectomy) secondary to the results of the FNAC is not recommended. Free hand FNAC might be a reason for the relatively high percentage of inconclusive results. Ultrasound guided FNAC can improve the yield of the puncture. On top of that pathological interpretation of the cytology is not always straight forward.

Related: Thyroid Cancer

Chera BS, Eisbruch A, Murphy BA, et al.
Recommended patient-reported core set of symptoms to measure in head and neck cancer treatment trials.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Related Publications
We identified a standard core set of patient-reported symptoms and health-related quality-of-life (HRQOL) domains to be assessed in head and neck (H&N) cancer clinical trials. The core symptom and HRQOL domain scores were used to guide recommendations by a working group of experts as part of a National Cancer Institute Symptom Management and HRQOL Clinical Trials Planning Meeting. A PubMed search was conducted using the search terms of "health-related quality of life" and "head & neck cancer," limited to publications from January 1, 2000, to December 31, 2010. Fifty-four articles were used to guide the choice of recommendations. Twenty-nine symptoms and nine domains were identified, from which 12 H&N-specific core symptoms and HRQOL domains were recommended: swallowing, oral pain, skin changes, dry mouth, dental health, opening mouth/trismus, taste, excess/thick mucous/saliva, shoulder disability/motion, voice/hoarseness, social domain, and functional domain. This core set of 12 H&N-specific, patient-reported symptoms and HRQOL domains should be assessed in future H&N cancer clinical trials.

Related: USA

Rafee S, Elamin YY, Cronin K, et al.
A rare case of nasopharyngeal carcinoma with widespread CNS metastases.
Ir Med J. 2014; 107(6):180-1 [PubMed] Related Publications
Nasopharyngeal cancer is unique among head and neck cancers. Despite definitive treatment, there is a high rate of recurrence, most commonly in the bone, lung or liver. Brain metastases and particularly, leptomeningeal carcinomatosis are extremely rare. We present a case of recurrent nasopharyngeal carcinoma with brain metastases and leptomeningeal carcinomatosis in the absence of local recurrence and systemic metastases.

Related: Nasopharyngeal Cancer

Galvin S, Healy CM
Oral hairy leukoplakia in healthy, immunocompetent individuals.
Ir Med J. 2014; 107(6):179-80 [PubMed] Related Publications
Oral hairy leukoplakia (OHL), while typically associated with HIV infection and immunosuppression, is rarely seen in HIV negative immunocompetent individuals. We report on two cases of OHL in immunocompetent patients.

Yang WC, Chen CH, Tang JY, et al.
Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by surgery and concurrent chemoradiotherapy improves outcome of recurrent advanced head and neck squamous cell carcinoma.
Anticancer Res. 2014; 34(7):3765-73 [PubMed] Related Publications
BACKGROUND: Locally recurrent rate of advanced head and neck squamous cell carcinoma (HNSCC) still remains high and the treatment is controversial.
PATIENTS AND METHODS: We retrospectively analyzed ninety-three patients with recurrent advanced oral cancer from 2009 to 2013. Sixty-four patients are in the docetaxel with cisplatin and 5'-fluorouracil (TPF) group and the remaining twenty-nine patients are in the cisplatin and 5'-fluorouracil (PF) group.
RESULTS: The overall response rate was better in the TPF group (p=0.005) than the PF group. Patients who received induction chemotherapy, TPF, followed by surgery and concurrent chemoradiotherapy (CRT) had better overall survival (OS) (p=0.012) and progression-free survival (PFS) (p=0.038), while patients with prior intra-arterial-infusion-chemotherapy had an adverse impact on OS (p=0.039).
CONCLUSION: We showed that induction chemotherapy with TPF, followed by surgery and consolidation CRT, is the ideal choice for recurrent advanced HNSCC with improving response rates and survival. However, prior intra-arterial-infusion-chemotherapy showed an adverse impact.

Related: Cisplatin Fluorouracil Docetaxel

Matsumoto H, Kubota H, Higashida M, et al.
Docetaxel/ TS-1 with radiation for unresectable squamous cell carcinoma of the esophagus--a phase II trial.
Anticancer Res. 2014; 34(7):3759-63 [PubMed] Related Publications
BACKGROUND: We tried a new regimen of docetaxel / TS-1 (tegafur-gimestat-otastat potassium) combined with radiation for squamous cell carcinoma of the esophagus in a phase II trial.
PATIENTS AND METHODS: The patients, whose tumor invaded other organs without other organ metastasis, were given TS-1 (60 mg/m2/day) from days 1 to 14, and docetaxel (20-30 mg/m2) on days 1 and 8. They received radiation in 2.0 Gy from days 1 to 21. Patients were given a seven-day rest after the first course, and then were treated with the same regimen from days 28 to 49.
RESULTS: Seventeen cases were enrolled in the study. The response rate was 76.4% (13/17). The overall 5-year survival rate was 29.6% (5/17) and median survival time was 15.2 months. Adverse events more than grade 3 occurred in 10 cases.
CONCLUSION: This combination therapy may be one of the most effective treatments because of its lower rate of non-hematological adverse events and higher response rate. Three cases also underwent salvage surgery when the tumor recurred, and in one case, chemoradiation to a metastatic nodule on the thoracic wall was added.

Related: Cancer of the Esophagus Esophageal Cancer Tegafur-uracil Docetaxel

Tsai CW, Chang WS, Lin KC, et al.
Significant association of Interleukin-10 genotypes and oral cancer susceptibility in Taiwan.
Anticancer Res. 2014; 34(7):3731-7 [PubMed] Related Publications
Interleukin-10 (IL10) is an immunosuppressive cytokine which may facilitate carcinogenesis by down-regulating interferon-gamma production and supporting tumor escape from the immune response. Polymorphisms within the promoter of IL10 gene may not only contribute to differential IL10 expression levels among individuals but also to oral cancer susceptibility. In this hospital-based study, the association of IL10 A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872) polymorphisms with oral cancer risk were examined. A total of 788 cases with oral cancer risk and 956 controls were genotypes and analyzed by polymerase chain reaction and restriction fragment length polymorphism. The results showed that there were significant differential distributions among oral cancer cases and controls in the genotypic (p=6.29×10(-11)) and allelic (p=2.80×10(-13)) frequencies of IL10 A-1082G. Individuals who carried the AG or GG genotype for IL10 A-1082G had a 1.90- and 3.27-fold higher risk, respectively, of developing nasopharyngeal carcinoma compared to those who carried AA genotype (95% confidence interval=1.51-2.39 and 1.95-5.47). None of the other two polymorphisms investigated appear to affect cancer risk. In gene-lifestyle interaction analysis, we provide first evidence showing of an obvious joint effect of IL10 A-1082G genotype with individual smoking and areca chewing habits on nasopharyngeal carcinoma risk. The AG and GG genotypes of IL10 A-1082G, together with smoking and areca chewing habits, synergistically contribute to individual susceptibility for oral cancer.

Related: IL10 Oral Cancer Nasopharyngeal Cancer

Sohda M, Sakai M, Honjyo H, et al.
Use of pre-treatment 18F-FAMT PET to predict patient survival in squamous cell carcinoma of the esophagus treated by curative surgery.
Anticancer Res. 2014; 34(7):3623-8 [PubMed] Related Publications
BACKGROUND: [18F]-3-fluoro-alpha-methyl tyrosine (18F-FAMT) as an amino acid tracer in positron emission tomography (PET) has been widely investigated in several tumor types. Herein we investigated the clinical significance of 18F-FAMT PET uptake as a prognostic marker together in our updated data of patients with esophageal cancer.
PATIENTS AND METHODS: We retrospectively assessed the treatment outcomes of 42 patients with histologically-confirmed esophageal cancer. The survival rate was analyzed using the median peak standardized uptake value (SUV) with 2.2 as the cut-off value.
RESULTS: FAMT uptakes were significantly correlated with factors reflecting tumor progression. Moreover, a significant correlation was observed between FAMT uptake and disease-free survival (p=0.023). Moreover, on evaluation of individual lymph node groups, the specificity and positive predictive value were significantly higher for 18F-FAMT-PET than for 18F-FDG-PET and computed tomography (CT).
CONCLUSION: 18F-FAMT is an important pre-treatment diagnostic modality and its accumulation is a good predictor of disease-free survival (DFS) in patients with operable esophageal cancer.

Related: Cancer of the Esophagus Esophageal Cancer

Sakurai T, Okumura H, Matsumoto M, et al.
Endoglin (CD105) is a useful marker for evaluating microvessel density and predicting prognosis in esophageal squamous cell carcinoma.
Anticancer Res. 2014; 34(7):3431-8 [PubMed] Related Publications
BACKGROUND: Angiogenic molecular markers such as vascular endothelial growth factor and tumor microvessel density reflect prognosis of human cancers. The present study clarified the usefulness of endothelial marker endoglin (CD 105) by assessing microvessel density in esophageal squamous cell carcinoma (ESCC).
MATERIALS AND METHODS: We immunohistochemically investigated CD105, CD31, and vascular endothelial growth factor-A VEGF-A expression in primary esophageal squamous cell carcinoma specimens from 142 patients.
RESULTS: Microvessel density was 35.9±21.2 for CD105 and 46.3±25.4 for CD31. CD105 microvessel density was significantly associated with tumor length, tumor invasion depth, lymph node metastasis, stage, lymphatic invasion, venous invasion, and VEGF-A expression; its correlation with almost all clinicopathological parameters was stronger than CD31 microvessel density. And significantly better prognosis was achieved in patients with low, compared to high CD105, microvessel density.
CONCLUSION: CD105 microvessel density reflected the degree of angiogenesis and prognosis in patients with esophageal squamous cell carcinoma.

Related: Cancer of the Esophagus Esophageal Cancer Angiogenesis and Cancer VEGFA

Saito H, Ando S, Morishita N, et al.
A combined lymphokine-activated killer (LAK) cell immunotherapy and adenovirus-p53 gene therapy for head and neck squamous cell carcinoma.
Anticancer Res. 2014; 34(7):3365-70 [PubMed] Related Publications
BACKGROUND: The antitumor activity of lymphokine activated killer (LAK) cells immunotherapy is not always effective in all patients, especially when used alone. In this study, we investigated the in vitro antitumor activities of a combination of LAK immunotherapy and gene therapy employing an adenovirus carrying the p53 gene (Ad-p53) in human head and neck squamous cell carcinoma.
MATERIALS AND METHODS: The in vitro cytotoxicity of LAK cells was tested in H891 cells infected with or without Ad-p53, and the mRNA expression levels of natural killer group 2D ligands (UL16 binding protein (ULBP) 1 to 5) and tumor necrosis factor (TNF-α) in these cells were measured by real-time reverse transcription polymerase chain reaction.
RESULTS: Ad-p53 infection increased the cytotoxicity of LAK cells against H891 cells, and also increased the mRNA expression levels of the ULBPs in H891 cells and TNF-α in the LAK cells.
CONCLUSION: The antitumor activities of LAK cells in H891 cells were enhanced by Ad-p53.
CONCLUSION: The combinational therapy of LAK immunotherapy and Ad-p53 gene therapy may represent a new paradigm for the treatment of head and neck cancer.

Related: Hypopharyngeal Cancer TNF TP53

Poi MJ, Knobloch TJ, Sears MT, et al.
Coordinated expression of cyclin-dependent kinase-4 and its regulators in human oral tumors.
Anticancer Res. 2014; 34(7):3285-92 [PubMed] Related Publications
BACKGROUND/AIM: While aberrant expression of cyclin-dependent kinase-4 (CDK4) has been found in squamous cell carcinoma of the head and neck (SCCHN), the associations between CDK4 and its regulators, namely, cyclin D1, cyclin E, gankyrin, SEI1, and BMI1 in gene expression remain to be explored. Herein we investigated the mRNA profiles of these oncogenes and their interrelations in different oral lesion tissues.
MATERIALS AND METHODS: Thirty SCCHN specimens and patient-matched high at-risk mucosa (HARM) and 16 healthy control specimens were subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses.
RESULTS: The mRNA levels of CDK4, cyclin D1, gankyrin, SEI1, BMI1 were significantly elevated in both HARM and SCCHN (in comparison with control specimens), and statistically significant correlations were found among these markers in gene expression.
CONCLUSION: Up-regulation of CDK4 and its regulators takes place in oral cancer progression in a coordinate manner, and HARM and SCCHN share a similar molecular signature within the CDK4-pRB pathway.

Related: Oral Cancer BCL1 Gene (CCND1)

Pérez-Mitchell C, Acosta JA, Ferrer-Torres LE
Robotic-assisted salvage supraglottic laryngectomy.
P R Health Sci J. 2014; 33(2):88-90 [PubMed] Related Publications
Traditional open surgery has historically been the standard approach to treating many head and neck conditions. The introduction of the first robot into the surgical world in 1985 has been a keystone in the development of minimally invasive surgical (MIS) techniques. Transoral robotic surgery (TORS) is a minimally invasive technique used for the treatment of head and neck pathologies, including benign and malignant lesions. When performed in select patients, TORS offers low post-operative morbidity, along with very few functional and cosmetic compromises. Herein, we present the first TORS supraglottic partial laryngectomy performed in Puerto Rico or in any region in Latin America. A 68-year-old male who had previously undergone radiation therapy presented with hoarseness and weight loss. A suspension microlaryngoscopy showed a lesion of the left false vocal cord; a biopsy was performed. The patient was diagnosed with a supraglottic squamous cell carcinoma (T2N0M0); the tumor was completely excised using TORS. No post-operative complications occurred.

Related: Cancer of the Larynx Laryngeal Cancer - Molecular Biology

Pickering CA, Mas J, Dykes JN, et al.
Exposure levels associated with Na(131)I thyroid cancer patients: correlation with initial activity and clinical physical parameters.
Health Phys. 2014; 107(2 Suppl 2):S163-5 [PubMed] Related Publications
Initial radiation exposure levels X (0) at 1 m from the navel of thyroid cancer patients were measured for 165 individuals at the time of ingestion. Some 61 patients had previously signed informed consent so only those patients could be assayed with regard to body parameters. While the activity was in the stomach, resultant X (0) values were seen to be linearly correlated with the total (131)I activity (A) given orally. Yet large differences in X (0) were seen; e.g., at A = 7.4 GBq, variations of a factor of four were found between the largest and smallest exposure rates. Correlation analyses were performed between normalized rate X (0)A-1 and several patient physical parameters. These included age, sex, height, weight, and BMI (body mass index). Only weight and BMI had significant linear correlation (p < 0.05) with normalized exposure rate. In the former case, the correlation coefficient ρ (weight) was -0.296 (p = 0.02). Using BMI as the independent variable, ρ (BMI) was -0.386 (p = 0.0021). With further analysis of the BMI variation, 95% confidence intervals could be determined at various BMI levels. For example, at 28 kg m(-2), the normalized rate varied between 0.039 and 0.0446 μGy h(-1) MBq(-1)-approximately a ±6.5% variation on the mean value of 0.0419 μGy h(-1) MBq(-1) at this BMI. Given such clinical information, differences in normalized exposure rate can be reduced to values on the order of ±10% or less for BMI values over the clinically relevant interval 20 to 40 kg m(-2).

Related: Thyroid Cancer

Twigt BA, van Dalen T, Vroonhoven TJ, Consten EC
Recurrent hyperparathyroidism caused by benign neoplastic seeding: two cases of parathyromatosis and a review of the literature.
Acta Chir Belg. 2013 May-Jun; 113(3):228-32 [PubMed] Related Publications
BACKGROUND: Parathyromatosis is defined as small nodules of hyperfunctioning parathyroid tissue scattered in the soft tissues of the neck and/or mediastinum. Parathyromatosis may be primary, it may be aimed for when autotransplanting parathyroid tissue in secondary hyperparathyroidism, and it may occur after surgery for primary hyperparathyroidism (pHPT). In the latter cases parathyromatosis poses a diagnostic and therapeutic challenge.
METHODS: To illustrate the clinical problem of parathyromatosis as a rare cause of recurrent disease after an operation for pHPT we describe two patients and performed a review of the literature for contributing factors.
RESULTS: Two patients, previously treated for pHPT and having undergone multiple neck explorations had at their final operation numerous small nests of benign parathyroid tissue scattered throughout connective tissue of the neck. These findings concur with various previous cases reported in the reviewed literature.
CONCLUSIONS: These cases illustrate that meticulous handling of parathyroid adenomas during surgical excision is of the utmost importance. Regardless of which operating technique is utilised, great emphasis must be placed on precautions towards ensuring the complete and above all the intact removal of the affected gland without capsular rupture. As parathymatosis is caused by seeding, which although extremely rare, it might very well result in the need for extensive reexploration.

Related: Parathyroid Cancer

Li X, Xu H, Ma H
Beclin 1 is highly expressed in papillary thyroid carcinoma and correlates with lymph node metastasis.
Acta Chir Belg. 2013 May-Jun; 113(3):175-81 [PubMed] Related Publications
BACKGROUND: Autophagy is believed to be important in tumorigenesis and tumor progression. The human beclin-1 gene, a key regulator of autophagy formation, located on chromosome 17q21, has been identified as the mammalian orthologue of Atg6 (autophagy-related gene) and may be a haploinsufficient tumor suppressor gene. Loss of expression or point mutation could serve as a mechanism of loss of beclin-1 tumor suppressor function in cancers. However, our recent study revealed that point mutation of the beclin-1 gene is a rare event in papillary thyroid carcinoma (PTC).
METHODS: We investigated the expression of beclin-1 in human PTC. Tissue samples from 86 cases of papillary thyroid carcinoma were used for the present study. 57 cases of papillary thyroid carcinoma were with lymph node metastasis. The expression of beclin-1 in tumor, normal tissue adjacent to tumor, distant normal tissue, metastatic lymph node and normal lymph node was examined with immunohistochemistry. The beclin-1 expression between tumor and normal tissue, metastatic and normal lymph node was also analyzed.
RESULTS: The expression of beclin-1 was detected in 88.4% (76/86) of the tumors and 98.2% (56/57) of metastatic lymph nodes. In contrast, normal tissues adjacent to tumor, distant normal tissues and normal lymph nodes showed no or very weak expression of beclin-1. Beclin-1 was significantly correlated with tumorigenesis and lymph node metastasis in human PTC.
CONCLUSIONS: High expression of beclin-1 in PTC and metastatic lymph node suggest that neo-expression of beclin-1 may play a role in tumorigenesis and lymph node metastasis in human PTC.

Related: Thyroid Cancer

Khalil Q, Gopalswamy N, Agrawal S
Missed esophageal and gastric cancers after esophagogastroduodenoscopy in a midwestern military veteran population.
South Med J. 2014; 107(4):225-8 [PubMed] Related Publications
OBJECTIVES: Esophagogastroduodenoscopy (EGD) with biopsy has become the standard procedure for diagnosing esophageal and gastric cancers (EGC) and is considered to have high sensitivity and specificity. To date, few studies have attempted to examine the rates of missed EGC after EGD and no study addresses the rate of missed EGC in a military veteran patient population. This led to us examine missed EGCs at our VA Medical Center across a 10-year period.
METHODS: An electronic database was used to identify patients who were diagnosed between 2000 and 2010 as having EGC. Missed cancers were defined as cancers diagnosed within 1 year of EGD, possible missed cancers as those diagnosed 1 to 3 years after EGD, and latent cancers as those diagnosed between 3 and 5 years after EGD.
RESULTS: A total of 94 patients fulfilled the study criteria: 69 had esophageal cancer and 25 had gastric cancer diagnosed at our institution during the study period. Of the included cases, one patient had a missed cancer (1.06%) and four patients had possible missed cancers (4.26%); no patients had latent cancer.
CONCLUSIONS: The true incidence of missed EGC in military veteran patients is not known. It is difficult to compare our findings to those of other studies because of the heterogeneity of studies. Our study echoes the findings of the others: EGD remains an important and effective tool in diagnosing EGC. At the same time, it also points out an important limitation, that EGC can be missed on EGD. Our findings also emphasize the importance of obtaining biopsies of any abnormality and timely clinical follow-up and by repeat EGD as needed.

Related: Cancer of the Esophagus Esophageal Cancer Stomach Cancer Gastric Cancer

Brito JP, Hay ID, Morris JC
Low risk papillary thyroid cancer.
BMJ. 2014; 348:g3045 [PubMed] Related Publications
Thyroid cancer is one of the fastest growing diagnoses; more cases of thyroid cancer are found every year than all leukemias and cancers of the liver, pancreas, and stomach. Most of these incident cases are papillary in origin and are both small and localized. Patients with these small localized papillary thyroid cancers have a 99% survival rate at 20 years. In view of the excellent prognosis of these tumors, they have been denoted as low risk. The incidence of these low risk thyroid cancers is growing, probably because of the use of imaging technologies capable of exposing a large reservoir of subclinical disease. Despite their excellent prognosis, these subclinical low risk cancers are often treated aggressively. Although surgery is traditionally viewed as the cornerstone treatment for these tumors, there is less agreement about the extent of surgery (lobectomy v near total thyroidectomy) and whether prophylactic central neck dissection for removal of lymph nodes is needed. Many of these tumors are treated with radioactive iodine ablation and thyrotropin suppressive therapy, which-although effective for more aggressive forms of thyroid cancer-have not been shown to be of benefit in the management of these lesions. This review offers an evidence based approach to managing low risk papillary thyroid cancer. It also looks at the future of promising alternative surgical techniques, non-surgical minimally localized invasive therapies (ethanol ablation and laser ablation), and active surveillance, all of which form part of a more individualized treatment approach for low risk papillary thyroid tumors.

Related: Thyroid Cancer

Minokadeh A, Wulkan AJ, Beer K, Waibel JS
Merkel cell carcinoma.
Skinmed. 2014 Mar-Apr; 12(2):120-1 [PubMed] Related Publications
A 92-year-old man presented for evaluation with a 1-month history of a rapidly growing asymptomatic pink nodule on his forearm. Biopsy results of the lesion demonstrated pathology consistent with Merkel cell carcinoma (MCC). Immunohistochemical studies displayed positive cytoplasmic staining for cytokeratin AE1/AE3, positive dot-like perinuclear staining for cytokeratin-20, diffuse cytoplasmic staining for neuron specific enolase, and no significant staining for S-100. Subsequent positron emission tomography did not reveal evidence of metastatic disease. Wide excision of the lesion was performed along with a sentinel node biopsy of his left axilla. The sentinel nodes were negative for MCC. Adjuvant radiation treatment of the tumor site was provided because the pathologist noted MCC within 2 mm of the deep margin.

Related: Merkel Cell Carcinoma Skin Cancer

Semple CJ, Killough SA
Quality of life issues in head and neck cancer.
Dent Update. 2014; 41(4):346-8, 351-3 [PubMed] Related Publications
UNLABELLED: Head and neck cancer (HNC) constitutes approximately 3% of all cancers in the UK, with in excess of 8500 new cases annually. Management of HNC depends on site, extent, histology, previous medical history and patient choice. A multidisciplinary approach is required to optimize patient wellbeing, owing to the significant functional and psychosocial implications that can impact on quality of life. Members of the dental team, to include the general dental practitioner, have a key role in patient care; therefore the dental team should be knowledgeable in the short-term and longer-term implications and how this impacts on quality of life.
CLINICAL RELEVANCE: This article offers the dental team with an overview of how HNC and the various treatments, such as surgery, radiotherapy and chemotherapy, impact upon quality of life, both in the short-term and longer-term.

Huq AH, Aktaruzzaman M, Habib MA, et al.
A comparative study between fine needle aspiration cytology findings and histopathological report of major salivary gland neoplasm in a tertiary hospital of Bangladesh.
Bangladesh Med Res Counc Bull. 2013; 39(2):69-73 [PubMed] Related Publications
Salivary gland tumours are relatively uncommon and most of the tumours arise from parotid gland. Fine needle aspiration cytology (FNAC) is advised preoperatively as diagnostic tool but sometimes found to shown both false positive and false negative results. This study was aimed to find out distribution of neoplasm of major salivary glands and also to explore the sensitivity and specificity of FNAC. The present cross sectional study was done in the Dept. of Otolaryngology Head and Neck Surgery, BSMMU from January 2007 to December 2008. A total number of 60 gender-matched patients with major salivary neoplasm, confirmed by FNAC, were recruited in the study. Operated salivary gland specimens were sent for histopathological examination, histopathological findings were compared. Overall male to female ratio was 1:1. Out of 60 cases, 47 (78.3%) patients had parotid and 13 (21.7%) patients submandibular gland neoplasm. Male to female ratio for parotid tumour was 1:1.1 and for submandibular 1.6:1. Mean age of the patients was 44.5 with range of 14-85 years. Of the total 60 cases 47 (78.3%) were benign and 13 (21.7%) malignant. Out of 47 parotid tumour 85.1% were benign and 14.9% malignant. Among the parotid tumour 97% were superficial lobe and 3.0% deep lobe. In case of submandibular gland 53.84% were benign and 46.15% tumour malignant. According to the sides of involvement, 25 (53.2%) cases of parotid neoplasm tumour were in the left and 22 (46.8%) the right. In submandibular gland the distribution was 7 (53.8%) and 6 (46.16%) respectively. Statistically incidence of parotid tumour was significantly higher than submandibular tumour (p < 0.05). Out of 60 cases in 56 (93.3%) preoperative FNAC and postoperative histopathological findings were same. There was 1.7% false positive and 5% were false negative results. Sensitivity, specificity of FNAC were 80% and 97.8% respectively. Positive predictive value was 92.3% and negative predictive 93.6% for FNAC.FNAC though cheap and safe but its diagnostic accuracy was 93.3%.Histopathologial examination remained to be of value for diagnostic confirmation of major salivary gland neoplasm.

Carcoforo P, Portinari M, Feggi L, et al.
Radio-guided selective compartment neck dissection improves staging in papillary thyroid carcinoma: a prospective study on 345 patients with a 3-year follow-up.
Surgery. 2014; 156(1):147-57 [PubMed] Related Publications
BACKGROUND: Prospective uncontrolled study to investigate in papillary thyroid carcinoma (PTC) patients: (1) Distribution of lymph node metastases within the neck compartments, (2) factors predicting lymph nodes metastases, and (3) disease recurrence after thyroidectomy associated with radio-guided selective compartment neck dissection (RSCND).
METHODS: We studied 345 consecutive PTC patients operated on between February 2004 and October 2011 at the S. Anna University Hospital, Ferrara (Italy). Patients with cervical lymph node metastases on preoperative ultrasonography and fine needle aspiration cytology were excluded. All patients underwent total thyroidectomy associated with SLN identification followed by RSCND in the SLN compartment, without SLN frozen section.
RESULTS: In patients with lymph node metastases, metastatic nodes were not in the central neck compartment in 22.6% of the cases. The presence of infiltrating or multifocal PTC was a predicting factor for lymph nodes metastases. The median follow-up was 35.5 months. RSCND was associated with a false-negative rate of 1.1%, a persistent disease rate of 0.6%, and a recurrent disease rate of 0.9%. The permanent dysphonia rate was 1.3%.
CONCLUSION: RSCND associated with total thyroidectomy may improve: (1) the locoregional lymph node staging, and (2) the identification of the site of lymphatic drainage within the neck compartments. Thus, considering the high false-negative rate of sentinel lymph node biopsy (SLNB), a radio-guided technique in PTC patients may guide the lymphadenectomy (ie, RSCND) to increase the metastatic yield and improve staging of the disease rather than avoid prophylactic lymphadenectomy (ie, SLNB).

Related: Thyroid Cancer

Onxley JD, Yoo DS, Muradyan N, et al.
Comprehensive population-averaged arterial input function for dynamic contrast-enhanced vmagnetic resonance imaging of head and neck cancer.
Int J Radiat Oncol Biol Phys. 2014; 89(3):658-65 [PubMed] Related Publications
PURPOSE: To generate a population-averaged arterial input function (PA-AIF) for quantitative analysis of dynamic contrast-enhanced MRI data in head and neck cancer patients.
METHODS AND MATERIALS: Twenty patients underwent dynamic contrast-enhanced MRI during concurrent chemoradiation therapy. Imaging consisted of 2 baseline scans 1 week apart (B1/B2) and 1 scan after 1 week of chemoradiation therapy (Wk1). Regions of interest (ROIs) in the right and left carotid arteries were drawn on coronal images. Plasma concentration curves of all ROIs were averaged and fit to a biexponential decay function to obtain the final PA-AIF (AvgAll). Right-sided and left-sided ROI plasma concentration curves were averaged separately to obtain side-specific AIFs (AvgRight/AvgLeft). Regions of interest were divided by time point to obtain time-point-specific AIFs (AvgB1/AvgB2/AvgWk1). The vascular transfer constant (Ktrans) and the fractional extravascular, extracellular space volume (Ve) for primaries and nodes were calculated using the AvgAll AIF, the appropriate side-specific AIF, and the appropriate time-point-specific AIF. Median Ktrans and Ve values derived from AvgAll were compared with those obtained from the side-specific and time-point-specific AIFs. The effect of using individual AIFs was also investigated.
RESULTS: The plasma parameters for AvgAll were a1,2 = 27.11/17.65 kg/L, m1,2 = 11.75/0.21 min(-1). The coefficients of repeatability (CRs) for AvgAll versus AvgLeft were 0.04 min(-1) for Ktrans and 0.02 for Ve. For AvgAll versus AvgRight, the CRs were 0.08 min(-1) for Ktrans and 0.02 for Ve. When AvgAll was compared with AvgB1/AvgB2/AvgWk1, the CRs were slightly higher: 0.32/0.19/0.78 min(-1), respectively, for Ktrans; and 0.07/0.08/0.09 for Ve. Use of a PA-AIF was not significantly different from use of individual AIFs.
CONCLUSION: A PA-AIF for head and neck cancer was generated that accounts for differences in right carotid artery versus left carotid artery, day-to-day fluctuations, and early treatment-induced changes. The small CRs obtained for Ktrans and Ve indicate that side-specific AIFs are not necessary. However, a time-point-specific AIF may improve pharmacokinetic accuracy.

Shiozaki H, Sudo K, Xiao L, et al.
Distribution and timing of distant metastasis after local therapy in a large cohort of patients with esophageal and esophagogastric junction cancer.
Oncology. 2014; 86(5-6):336-9 [PubMed] Article available free on PMC after 07/06/2015 Related Publications
BACKGROUND: Patients with localized esophageal and esophagogastric junction cancer (EAC) receive chemoradiation and then surgery (trimodality, TMT) or definitive chemoradiation (bimodality, BMT). Distant metastases (DMs) are common but the details of their distribution and timing in a large cohort have not been described.
METHODS: 629 patients with localized EAC who had TMT or BMT were analyzed. Standard statistical methods were used to define the end points.
RESULTS: The median follow-up time was 37.2 months (interquartile range 17.8-65.0). Of 356 TMT patients, 33% (119) developed DM as their first relapse and of 273 BMT patients, 40% (109) developed DM; 91% (TMT) and 96% (BMT) of the DMs were diagnosed within 2 years of local therapy. The most common sites of DM were: lung, distant nodes, liver, peritoneal cavity, bone, brain and pleura in order of frequency. The median overall survival of TMT patients with DM was 10.2 months (95% CI 7.8-12.7) and that for BMT patients with DM was 7.8 months (95% CI 5.7-9.9).
CONCLUSIONS: Following TMT or BMT, ≥33% of patients developed DMs and most of these occurred within 2 years (>90%) of local therapy. A clinical model is desirable that associates clinical parameters with a high risk for DM in TMT-eligible patients prior to surgery.

Related: Cancer of the Esophagus Esophageal Cancer

Tanaka N, Yamashita T, Yamamoto S, et al.
Histological growth pattern of and alpha-actinin-4 expression in thyroid cancer.
Anticancer Res. 2014; 34(6):3157-63 [PubMed] Related Publications
AIM: To assess the clinicopathological significance of the histological growth pattern (HGP) and α-actinin-4 (ACTN4) expression in thyroid cancer.
PATIENTS AND METHODS: We classified 83 thyroid cancer cases into infiltrative margin (IM) and pushing margin (PM) groups according to peripheral tumor margin contour and immunohistochemically determined ACTN4 expression. Correlations between clinical stage and clinicopathological characteristics were analyzed.
RESULTS: IM and high ACTN4 expression were observed in 39% and 49% of cancer cases, respectively. Higher clinical stage was significantly correlated with older age, higher T and N factor, preoperative recurrent laryngeal nerve paralysis (pre-RLNP), IM, and poor prognosis. Patients with stage IV disease had significantly poorer prognosis than those with stages I-III. On multivariate analysis, older age, pre-RLNP, and IM correlated with higher clinical stages. IM was significantly correlated with high ACTN4 expression.
CONCLUSION: IM, pre-RLNP, and ACTN4 expression could be novel indicators of tumor aggression and prognostic factors of thyroid cancer.

Related: Thyroid Cancer

Tsai CW, Chang WS, Liu JC, et al.
Contribution of DNA double-strand break repair gene XRCC3 genotypes to oral cancer susceptibility in Taiwan.
Anticancer Res. 2014; 34(6):2951-6 [PubMed] Related Publications
The DNA repair gene X-ray repair cross complementing protein 3 (XRCC3) is thought to play a major role in double-strand break repair and in maintaining genomic stability. Very possibly, defective double-strand break repair of cells can lead to carcinogenesis. Therefore, a case-control study was performed to reveal the contribution of XRCC3 genotypes to individual oral cancer susceptibility. In this hospital-based research, the association of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539, rs28903081 genotypes with oral cancer risk in a Taiwanese population was investigated. In total, 788 patients with oral cancer and 956 age- and gender-matched healthy controls were genotyped. The results showed that there was significant differential distribution among oral cancer and controls in the genotypic (p=0.001428) and allelic (p=0.0013) frequencies of XRCC3 rs861539. As for the other polymorphisms, there was no difference between case and control groups. In gene-lifestyle interaction analysis, we have provided the first evidence showing that there is an obvious joint effect of XRCC3 rs861539 genotype with individual areca chewing habits on oral cancer risk. In conclusion, the T allele of XRCC3 rs861539, which has an interaction with areca chewing habit in oral carcinogenesis, may be an early marker for oral cancer in Taiwanese.

Related: Oral Cancer Polymorphisms

Yu CC, Hung SK, Liao HF, et al.
RAD001 enhances the radiosensitivity of SCC4 oral cancer cells by inducing cell cycle arrest at the G2/M checkpoint.
Anticancer Res. 2014; 34(6):2927-35 [PubMed] Related Publications
BACKGROUND: Inhibition of mammalian target of rapamycin (mTOR) kinase enhances the radiosensitivity of some cancer cells. We investigated the effect of RAD001, an mTOR inhibitor, on irradiated oral cancer cell lines.
MATERIALS AND METHODS: Clonogenic assays were performed to determine the radiosensitivity of SCC4 and SCC25 cells after treatment with RAD001. Target protein phosphorylation, apoptosis, and cell-cycle progression were assessed in SCC4 cells treated with RAD001 with and without ionizing radiation.
RESULTS: RAD001 increased the radiosensitivity of SCC4 cells without affecting cell death; it also inhibited phosphorylation of mTOR, S6, and factor 4E binding protein 1 and reduced the clonogenic survival of irradiated cancer cells. RAD001 combined with radiation increased G2 arrest by activating CHK1, which phosphorylates CDC25C at Ser216, thereby inhibiting CDC2-cyclin B 1 complex formation.
CONCLUSION: RAD001 enhances the radiosensitivity of SCC4 cells by inhibiting mTOR signaling and inducing G2 cell-cycle arrest through disruption of the G2 checkpoint.

Related: Apoptosis Signal Transduction Everolimus (Afinitor)

Ijichi K, Adachi M, Ogawa T, et al.
Cell-cycle distribution and Thymidilate Synthatase (TS) expression correlate with 5-FU resistance in head and neck carcinoma cells.
Anticancer Res. 2014; 34(6):2907-11 [PubMed] Related Publications
BACKGROUND: Acquired chemoresistance to 5-fluorouracil (5-FU) remains one of the obstacles for the success of 5-FU-based cancer chemotherapy, and some molecular mechanisms of acquired 5-FU resistance are still unknown. The main action of 5-FU is the suppression of DNA replication by inhibiting Thymidylate Synthase (TS).
MATERIALS AND METHODS: We analyzed 5-FU resistance mechanisms using the head and neck squamous cell carcinoma cell lines, UM-SCC-23, and two different resistant cell lines, UM-SCC-23/WR and UM-SCC-23/MR, which were procured from UM-SCC-23 cells. To acquire resistance, the two cells underwent repeated treatment of 5-FU with different durations and frequency. We determined differences in the cell-cycle distribution and the expression of TS proteins in the three cell lines. Moreover, cell-cycle distribution in cells which acquired resistance after 5-FU treatment, was compared to that of parental cells, using flow cytometric analysis.
RESULTS: There was a remarkable increase in TS protein expression levels in UM-SCC-23/WR following 5-FU treatment. S-phase cells of UM-SCC-23 and UM-SCC-23/WR cells were immediately increased after treatment with 5-FU, whereas UM-SCC-23/MR were accumulated to the S-phase slightly later.
CONCLUSION: The cell-cycle perturbation or elevation of TS protein expression may be involved in acquired 5-FU resistance and identifies 5-FU resistance mechanisms in the two different 5-FU treatment regimens.

Related: Fluorouracil

Omoto I, Matsumoto M, Uchikado Y, et al.
Immunohistochemical evidence of association between ghrelin expression and tumor growth in esophageal carcinoma.
Anticancer Res. 2014; 34(6):2727-33 [PubMed] Related Publications
BACKGROUND: Ghrelin, an orexigenic peptide, is primarily produced and secreted by the gastrointestinal tract. As far as we are aware of, there is no evidence of ghrelin expression in esophageal squamous cell carcinoma (ESCC).
MATERIALS AND METHODS: Two hundred and ten patients with ESCC who underwent surgical resection were enrolled in this study. We immunohistochemically investigated ghrelin expression in primary ESCC specimens and analyzed the relationship with clinicopathological factors.
RESULTS: High ghrelin expression was observed in 61 patients (29.0%). Depth of tumor invasion and histological differentiation were statistically associated with ghrelin expression. As for depth of tumor invasion, the deeper it was, the higher was the expression of ghrelin. Well-differentiated tumors had a significantly higher proportion of ghrelin-expressing cells than other types.
CONCLUSION: Ghrelin expression correlated with tumor depth and tumor differentiation, suggesting an important role of ghrelin in tumor growth in ESCC.

Related: Cancer of the Esophagus Esophageal Cancer

Kesselring R, Thiel A, Pries R, et al.
The complement receptors CD46, CD55 and CD59 are regulated by the tumour microenvironment of head and neck cancer to facilitate escape of complement attack.
Eur J Cancer. 2014; 50(12):2152-61 [PubMed] Related Publications
BACKGROUND: Membrane-bound complement restriction proteins (mCRPs) CD46, CD55 and CD59 enable tumour cells to evade complement dependent cytotoxicity and antibody-dependent killing mechanisms. But less is known about the role of these mCRPs in head and neck cancer.
METHODS: In this study we determined the expression of the mCRPs on head and neck squamous cell carcinoma (HNSCC) cell lines, on tumour tissue and TDLNs (tumour-draining lymph nodes) as well as on lymphocytes from HNSCC patients. The influence of the HNSCC microenvironment on the mCRP regulation was analysed using Flow Cytometry, Western blotting and small interfering RNAs (siRNA) transfection studies.
RESULTS: We examined the effects of the HNSCC tumour milieu on the expression levels of CD46, CD55 and CD59. We investigated the susceptibility of HNSCC cells to CDC (complement-dependent cytotoxicity) while silencing the mCRPs. Our results demonstrate a huge influence of the HNSCC tumour microenvironment on the regulation of mCRP expression and show a reciprocal regulation between the different mCRPs themselves.
CONCLUSIONS: In summary, our data indicate that HNSCC has evolved different strategies to evade complement attacks and that the tumour microenvironment leads to the enhancement of complement resistance of the surrounding tissue.

Related: Oral Cancer

Huang J, Zhang SY, Gao YM, et al.
MicroRNAs as oncogenes or tumour suppressors in oesophageal cancer: potential biomarkers and therapeutic targets.
Cell Prolif. 2014; 47(4):277-86 [PubMed] Related Publications
MicroRNAs are a class of small, non-coding RNAs that can negatively regulate protein-coding genes, and are associated with almost all known physiological and pathological processes, especially cancer. The number of studies documenting miRNA expression patterns in malignancy continues to expand rapidly, with continuously gained critical information regarding how aberrantly expressed miRNAs may contribute to carcinogenesis. miRNAs can influence cancer pathogenesis, playing a potential role as either oncogenes or tumour suppressors. Recently, several miRNAs have been reported to exert different regulatory functions in oesophageal cancer - the carcinoma typically arising from the epithelial lining of the oesophagus. These miRNAs also have potential clinical applications towards developing biomarkers or targets for possible use in diagnosis or therapy in oesophageal cancer. In this review, we have summarized the two (oncogenic or tumour suppressive) roles of miRNAs here, and their applications as potential biomarkers or therapeutic targets, which may illuminate future treatment for oesophageal cancer.

Related: Cancer of the Esophagus Esophageal Cancer

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